Evaluation of selective inhibitors of 11¦Â-HSD1 for the treatment of hypertension

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• 作者：David R. Bauman^a ; ^&dagger ; ; Alan Whitehead^b ; ^&dagger ; ; Lisa C. Contino^c ; Jisong Cui^a ; Margarita Garcia-Calvo^d ; Xin Gu^b ; Nancy Kevin^b ; Xiuying Ma^c ; Lee-yuh Pai^c ; Kashmira Shah^c ; Xiaolan Shen^e ; Sloan Stribling^c ; Hratch J. Zokian^d ; Joe Metzger^c ; Diane E. Shevell^a ; ^{diane_shevell@merck.com} ; Sherman T. Waddell^b ; ^{tim_waddell@merck.com}
• 关键词：11¦Â-HSD1 ; Hypertension ; 1 ; 2 ; 4-Triazoles ; 11¦Â-HSD1-KO ; Spontaneous hypertensive rat
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 June, 2013
• 年：2013
• 卷：23
• 期：12
• 页码：3650-3653
• 全文大小：517 K

文摘

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11¦Â-HSD1 inhibitors, we examined a set of 11¦Â-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11¦Â-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11¦Â-HSD1 independent pathway.